Apoptosis imaging with PET-18F-ML-10 for early assessment of response of brain metastases to radiotherapy

Objectives Imaging of apoptosis may provide real time information on the biological effect of anti-cancer treatment and may allow personalized treatment for individual patients. ¹⁸F-ML-10 is a novel, compact PET-tracer for apoptosis (α-methyl ¹⁸F-alkyl-dicarboxylic acid, MW=206). Since apoptosis is an early and prominent effect of radiation, we prospectively compared early changes detected by ¹⁸F-ML-10 with tumor response in patients with brain metastases undergoing radiotherapy.

Methods 10 patients with brain metastases underwent PET ¹⁸F-ML-10 before whole brain radiotherapy (10X3Gy) and on day 9-10 of treatment. The percentage of voxels in which uptake changed was determined by a voxel-based analysis and compared with change in tumor size per MRI 6-8 weeks post-treatment.

Results Seven patients completed the study. Reduction in tumor size (WHO criteria) was 25%-88%. Specific uptake of ¹⁸F-ML-10 was observed in all lesions, with marked, heterogenic changes between pre- and post-treatment images indicating a differential effect on various tumor sub-regions. A correlation of R²=0.82 (p=0.0049) was calculated between the percent of changed voxels and tumor shrinkage.

Conclusions ¹⁸F-ML-10 PET imaging of apoptosis in brain metastases produced clear images of both endogenous and irradiation-induced apoptosis. Correlation between ¹⁸F-ML-10 images and tumor radiographic response showed a significant correlation indicating a possible role for ¹⁸F-ML-10 in real-time monitoring the effect of radiotherapy in individual patients.